Pazufloxacin 注射液の投与量増加のための臨床第I 相試験.pdf

=Oqv4&15j1BVGMPYBDJOwd)CwhwH*gfJG0fJRD!RD!g1BVGMPYBDJO1；9wd)CwhwH*ghbsj|1；9aNpHR0tNHS|NHosd)s|tNHsc033|Sd)|aNpHR0tNHsc033|Sd)|aNp0tNHsc033|Sd)w6S|QU|hd)MOxMc:#iqh6aNpwNH|NHS|NHosd)p|$NBYqd)qwtQUhU|6$pxQxsTlhaNpwNH:#iwd)w6$x|HRpxHISc033N-|pxHISc033N-pKlhw$DSwx6$GVXbqQhh|NHsc033Sd)wBZSxHRS|Mcd)Ltx6ta|d)pwuQxsTlhQaNtNHosd)pwmS|Wsr|NHosd)pWtwmS|WsrwUCqhNHSd)pWS|(t|Wt|s|twtw?TwUCqhhd)hOsxsTlhU|UhhHRqSpKaNt!|XU|bqqhaNtNHSd)pHRpxtEt|(|WS|4wUCq|pxBtEtB|(|70-/01BVGMPYBDJOwd)CwhwH*gFig.1.Chemicalstructureofpazufloxacinmesilate.NCOOHCH3OOFH2NHCH3SO3HTable1.Subjectssummariesforpopulationpharmacokineticanalysishighmultipledoseinelderlyhighmultipledoseinnon-elderlyhighsingleandmultipledosesinnon-elderlyClassificationmultiplemultiplemultiplesingle1,0001,0001,0002,0001,500dose(mg)108777n69.73.523.33.722.63.224.33.622.13.3meanSDAge(yr)69.522.021.022.020.0Median65,7520,3020,2921,3120,27min,max165.55.0169.94.2169.96.3169.44.4173.43.2meanSDHeight(cm)165.1169.5172.3168.5173.4median159.9,175.0163.1,176.8157.4,175.4164.7,175.9168.9,179.4min,max61.26.861.47.162.88.859.76.264.77.8meanSDWeight(kg)58.759.761.357.364.8median52.4,70.053.0,72.553.4,76.652.5,70.654.6,79.2min,max22.32.321.21.721.72.220.92.521.41.9meanSDBMI(kg/m2)22.321.521.620.221.7median19.1,26.119.1,23.719.5,24.918.4,24.819.1,24.6min,max104.119.5117.617.2147.431.7124.918.7138.420.4meanSDCcr(mL/min)102.7114.9157.0126.0136.0median75,139102,154105,18399,144106,174min,maxwjqsOw&wtxMhloSc|wOQt0bX|sLhwMfUoMh1,1%w:T%wLxt6$c033.*$qsbqUoS|d)wCxQqQoMNxCR|OQt；|QUoM=OqTx|NxOQt0o0pVNqnZqwQT|QU-pVcpBhOQt0|sQ84bX|；pVOtqwAlUDtG|tZhfp|OQt0o|ttLhtd)C|bsj|NHsc033d)w；O；Cbq-hhpt|1；9NHsc033d)pxNtwOGs；xCqoSc|QxhqQoMwqT|1；9wd)CwhwH*g|6S|QU|hsS|gxwg*q*3#wqqt|wgww,j($1RDHoohI0qMOgaNpw；osS|SgxTp|aNpw；SgS|；Sgx；Fphggwtqj|gt($1p0tmMoGt|tgCwTphfw|U*pgt&pKqQhg0qhg|d)|d)MOS|d)8g1；9aNx|N-t1；9qoNHNHb；MhaNx|N-t1；9qoNHNHbN-；Mhd)|d)MOS|d)8aNpw；osS|SgHR0t:#ipwNHosd)x|NHosd)x|NHsc033|Sd)xphaNpw；SgHR0t:#ipwNHsc033|Sd)x1；9|phsS|d)S|d)x=Oqv4&15Table2.ScheduleofsingledosestudyFollow-up81211ScreeningDay28to2TimeInformedconsentSubjectbackgroundHospitalizationDrugadministrationInvestigatorexaminationVitalsigns(bloodpressure,pulserate,respiratory,temperature)12-leadelectrocardiogramImmunologicaltestClinicallaboratorytestHematology,bloodbiochemistry,urinalysisSerumPharmacokineticmonitoringUrineCrystalluria滑害害害害害害害害害害害害害害葛AdverseeventsDischarge24(hr)12(hr)11(hr)8(hr)6(hr)4(hr)3(hr)2(hr)90(min)75(min)65(min)60(min)30(min)0(min)60(min)DrugadministrationInvestigatorexamination12-leadelectrocardiogramClinicallaboratorytestVitalsigns(bloodpressure,pulserate,respiratory,temperature)SerumPharmacokineticmonitoringUrineCrystalluria滑害害害害害葛滑害害葛滑害害害害害害害害害害害害害害害害葛滑害害害害害葛滑害害葛滑害害葛滑害害害害害葛滑害害葛滑害害葛滑害害害害害害害害害害害害害害害害葛滑害害害害害葛滑害害葛滑害害葛s|d)xsd)qhaNpw；Sg0t:#ipwNHsc033|Sd)x1；9|phsS|d)S|d)xs|d)xsd)qhhgqwd)|g:|.O|#PEZNBTTJOEFY#.*S|$DS5BCMFth*S|*8aNpw；osS|Sg|aNpw；SgS|；SgwU*s|tosrw5BCMFS|5BCMFthgQw*gd)tQ|D|.O|7|7|,S|fwOS|wgCw|gd)wN；w|U*S|U*wBw|pww*hU*S|oaNpw；osS|Sg|aNpw；SgS|；SgwU*s|to5BCMFthFw8to|?$|U*B$U*|B=$U*|U*|B$U*|By%:zu:S|.9S|AolhSU.wJaNpw；osS|SgBwx|osd)pxd)S|d)w-pN-qh5BCMFSd)pxd)xd)S|d)w-|xd)S|d)w-|txd)S|d)w-pN-qh5BCMF70-/01BVGMPYBDJOwd)CwhwH*gTable3.ScheduleofmultipledosestudyFollow-up121a)131b)7b)6543211ScreeningDay28to2TimeInformedconsentSubjectbackgroundHospitalizationb)DrugadministrationInvestigatorexaminationVitalsigns(bloodpressure,pulserate,respiratory,temperature)12-leadelectrocardiogramImmunologicaltestClinicallaboratorytesta)Hematology,bloodbiochemistry,urinalysisSerumPharmacokineticmonitoringUrineCrystalluriaDischarge滑害害害害害害害害害害害害害害害害害害害害害害葛Adverseeventsa)highmultipledoseinnon-elderlywith1%PZFXb)highmultipledoseinnon-elderlyandelderlywith0.5%PZFX(Continued)wx|osd)pxd)|d)|Sd)pxd)xd)|d)|t|d)xd)|t|d)xd)|tN-qh5BCMFS|5BCMFJJaNpw；SgS|；SgBwx|d)xd)|d)w-|d)xd)|d)w|d)txd)|d)w-pN-qh5BCMFwx|d)xd)|d)|t|d)xd)|t|d)xd)|tN-qh5BCMFMOhBxmSQN|oBZm|hxqhT,jnX!x!qsTlhh|wUTtsp*lhtmMox|gwj|；|；O|Nd)qCqqw$srTgqwLTtK|K|KTsMS|swpQhgqwLU|TtK|KhxKTsMqQhw；qolhh|wSxtgtSZ；|U*wQ,jt0S|sShxOSwpQhsS|x*$)M；B.FE%3c033+WFSt,nV,1SFGFSSFE5FSN15t8Q|CqSB-hrs6rs6tsMrsO；Mo|$NBY|6$|7=Oqv4&15Table3.(continued)Day2424(hr)13(hr)12(hr)11(hr)8(hr)6(hr)4(hr)3(hr)2(hr)90(min)75(min)65(min)60(min)30(min)0(min)60(min)DrugadministrationInvestigatorexaminationVitalsigns(bloodpressure,pulserate,respiratory,temperature)12-leadelectrocardiogramClinicallaboratorytesta)SerumPharmacokineticmonitoringUrinea)Day3onlyDay524(hr)13(hr)12(hr)11(hr)8(hr)6(hr)4(hr)3(hr)2(hr)90(min)75(min)65(min)60(min)30(min)0(min)60(min)DrugadministrationInvestigatorexaminationVitalsigns(bloodpressure,pulserate,respiratory,temperature)12-leadelectrocardiogramClinicallaboratorytestSerumPharmacokineticmonitoringUrineCrystalluria(Continued)滑害害害害害害葛(1)Highsingleandmultipledosesinnon-elderlywith1%PZFXDay124(hr)13(hr)12(hr)11(hr)8(hr)6(hr)4(hr)3(hr)2(hr)90(min)75(min)65(min)60(min)30(min)0(min)60(min)DrugadministrationInvestigatorexaminationVitalsigns(bloodpressure,pulserate,respiratory,temperature)12-leadelectrocardiogramSerumPharmacokineticmonitoringUrineCrystalluria滑害害害害害害葛滑害害葛滑害害葛滑害害害害害害害害害害害害害害害害葛滑害害害害葛滑害害葛滑害害葛滑害害害害葛滑害害害害葛滑害害葛滑害害害害害害害害害害害害害害害害葛滑害害害害葛滑害害葛滑害害葛滑害害害害害害葛滑害害葛滑害害害害害害害害害害害害害害害害葛滑害害害害害害害害害害害害害害害害葛滑害害害害害葛滑害害害害害害害害害害害害害害害害害葛滑害害害害葛滑害害葛滑害葛滑害害害害葛滑害害害害害葛滑害害害害害害害害害害害害害害害害害葛滑害害害害葛滑害害葛滑害葛BZSxa5NBY|5c033|!=.wp63|$-|$-S|:y.35|0u7EZhhi|$NBY|5NBYxBZS；Mh$NBYS|6$；Mh6wQwU|$NBY|6$!:|d)!:9qhfgw!:0:!h；Mwposslh-PH:-PH9w*wU|Oqqt|wTUt|；tzQKqQhh|$NBY|6$#.*S|.Op4Y|0:!htmMo7tU|hBZS*tSd)w6wU|osd)wBZS*；MhOvdOt|sSd)wM|Sd)w6tSZ7BZS$TTNBYS|7BZS$TTNJO*|qwzt6xaQh70-/01BVGMPYBDJOwd)CwhwH*gTable3.(continued)(2)Highmultipledoseinnon-elderlyandelderlywith0.5%PZFXDay124(hr)12(hr)8(hr)6(hr)4(hr)3(hr)2(hr)90(min)75(min)65(min)60(min)30(min)0(min)PreDrugadministrationInvestigatorexaminationVitalsigns(bloodpressure,pulserate,respiratory,temperature)a)12-leadelectrocardiogramSerumPharmacokineticmonitoringUrineCrystalluriab)a)highmultipledoseinelderlywith0.5%PZFXonlyb)highmultipledoseinnon-elderlywith0.5%PZFXonly滑害害害害害害葛滑害害害害害害害害害害害害害害害害害葛滑害害害害害葛滑害害害葛滑害害葛滑害害葛滑害害葛滑害害害害害害害害害害害害害害害害害害害害害害害害害害葛Day2524(hr)13(hr)12(hr)2(hr)60(min)30(min)0(min)60(min)Drugadministrationa)Investigatorexaminationa)Vitalsigns(bloodpressure,pulserate,respiratory,temperature)12-leadelectrocardiograma)Clinicallaboratorytestb)SerumPharmacokineticmonitoringUrinea)highmultipledoseinelderlywith0.5%PZFXonlyb)Day4only滑害害害害害害葛滑害害葛滑害害害害害害害害葛滑害害葛滑害害害害害葛Day624(hr)12(hr)8(hr)6(hr)4(hr)3(hr)2(hr)90(min)75(min)65(min)60(min)30(min)0(min)60(min)DrugadministrationInvestigatorexaminationVitalsigns(bloodpressure,pulserate,respiratory,temperature)a)12-leadelectrocardiogramClinicallaboratorytestSerumPharmacokineticmonitoringUrineCrystalluriab)a)highmultipledoseinelderlywith0.5%PZFXonlyb)highmultipledoseinnon-elderlywith0.5%PZFXonly滑害害害害害害害害害害害害害害害害害葛滑害害害害葛滑害葛滑害葛滑害葛滑害葛滑害害害害害害害害害害害害害害害害害害害害害害害害害葛滑害害害害害葛?$?$T%:)3|33|13|234|25|254Y25DS|25Dd)Tw25Dw!=wAw-Zhh|25DwZx#BFUUwMOS|SJEFSJDJBwMO；Mh25DS|25DwOt|g:B-h25DNTFD|NTFD|NTFD|NTFD25DNTFDS|d)w-|NHosd)pxd)；w|NHSd)pxd)w6rs0ThBZS*S|6aNpw；osS|SgHR0tNHS|NHwosd)s|tNHSd)wssd)wBZSw*JHt|65BCMFth1；9NH|NHS|NHosd)w$NBYj)xfg|S|Hc033N-|6$j)xfg|S|HIc033N-pKlh$-Sj)xfg|S|-c033ISpK|NHS|NHd)px7pKlhU|NHd)pxh7E7tNHd)pxh$NBYS|6$w0:!$!:|d)w0:!:9qoosslh$NBYS|6$ww*xfgS|pKlhwTx$NBYpxq|d)qwtQUhU|6$pxqc|=Oqv4&15Fig.4.PZFXpharmacokineticparametersanddoseaftersingledose.(Xdose,Ypar